This invention is generally in the field of capillary electrophoresis, and relates particularly to a system for and a method of cooling the capillaries of a multiplexed or xe2x80x9cparallelxe2x80x9d capillary electrophoresis system.
Capillary electrophoresis (CE) is a chemical separation technique involving the use of one or more capillary tubes. Parallel CE, a recently developed technique using many parallel capillary tubes, is growing in popularity since this technology allows multiple samples to be analyzed quickly and efficiently. This is particularly advantageous in combinatorial chemistry where many hundreds and even thousands of samples are analyzed over a short period of time. Parallel CE involves the use of a xe2x80x9cbundlexe2x80x9d of capillary tubes, e.g., 96 such tubes. A chemical sample to be analyzed is loaded in each tube, and a high voltage is applied to the tube, causing the components of the sample to migrate in the tube at different speeds, thereby causing separation of the components which can then be analyzed by conventional light absorption or other techniques. Reference may be made to the following patents and publications for a more detailed description of CE, including parallel CE, and various analytical techniques used in CE: U.S. Pat. Nos. 5,900,934, 5,324,401, 5,312,535, 5,303,021, 5,239,360; C. Culbertson et al., Analytical Chemistry, 70, 2629-2638 (1998); and X. Gong et al., Analytical Chemistry, 71(2a); 4989-4996 (1999). None of these publications disclose the use of parallel CE to achieve chiral separation.
The electrical current passing through the parallel capillary tubes of a CE system can generate a substantial amount of heat, particularly where high voltages and electrical currents are used to achieve the separation of the samples, as in a chiral separation process using chiral buffers. If not dissipated, this heat can cause the formation of bubbles in the samples, sparking, and other undesirable results having an adverse affect on separation and analysis. Therefore, there is a need for a system for effectively cooling such tubes.
Among the several objects of this invention may be noted the provision of a multiplexed (parallel) CE system for effecting chiral separation at higher throughput; the provision of such a system with cooling apparatus sufficient to prevent overheating of the capillary tubes and contents thereof during chiral separation and other processes generating substantial heat; the provision of such a system and cooling apparatus which has no adverse affect on the separation and/or analytical process; the provision of such cooling apparatus which is adjustable to various cooling temperatures; the provision of such cooling apparatus which can be configured to remove a desired amount of heat; the provision of such apparatus which is safe to use.
In general, this invention is directed to a multiplexed capillary electrophoresis system with cooling sufficient to prevent overheating during separation. The system comprises a bundle of capillary tubes having inlet end portions spaced apart for loading of fluid samples to be analyzed into the tubes, outlet end portions for exit of the fluid samples from the tubes, and intermediate portions between the inlet and outlet end portions arranged in a generally planar array in which the intermediate portions extend side-by-side in closely spaced generally parallel relation. The system includes a power source adapted for applying a potential difference between the inlet end portions and the outlet end portions to cause an electrical current to flow through the contents of the capillary tubes at a level sufficient to cause separation in the fluid samples, the current generating heat in the tubes and the contents thereof. A light source is provided for directing light to pass through the generally planar array of intermediate portions of the capillary tubes, and a photodetector is provided for receiving light passing through said array. A thermally insulated enclosure encloses the bundle of capillary tubes, light source and photodetector. The system further comprises a heat transfer system for cooling the array and the inlet end portions of the capillary tubes to an extent sufficient to prevent overheating of the tubes and contents thereof due to said heat. In the preferred embodiment, this system includes a first heat transfer mechanism for cooling the array of closely spaced intermediate portions of the capillary tubes, and a second heat transfer mechanism for cooling the spaced apart inlet end portions of the capillary tubes.
In another aspect, this invention is directed to a multiplexed capillary electrophoresis system comprising a bundle of capillary tubes having inlet end portions positioned for loading of fluid samples to be analyzed into the tubes, outlet end portions for exit of said samples from the tubes, and intermediate portions between the inlet and outlet end portions arranged in an array in which the intermediate portions extend side-by-side in closely spaced generally parallel relation. The system includes a power source for applying a potential difference between the inlet end portions and the outlet end portions to cause an electrical current to flow through the contents of the capillary tubes at a level sufficient to cause separation in said fluid samples. A light source is provided for directing light to pass through the array of intermediate portions of the capillary tubes, and a photodetector receives light passing through the array. A heat transfer system is provided for cooling the array and the inlet end portions of the capillary tubes to an extent sufficient to prevent overheating of the tubes and contents thereof due to heat generated during separation. A thermally insulated enclosure encloses the bundle of capillary tubes, light source, photodetector, and said heat transfer system.
In one embodiment, a multiplexed capillary electrophoresis system of this invention comprises a conduction heat transfer mechanism for cooling the aforementioned array of closely spaced intermediate portions of the capillary tubes. The conduction heat transfer mechanism comprises a body of thermally conductive material having a length, a width, and a cooling face adapted to extend across substantially the entire width of the bundle for cooling the capillaries of the bundle. The cooling face is electrically insulated from the capillaries. A window is provided in the body for exposing the array.
The present invention is also directed to a method of preventing overheating of a bundle of capillary tubes during a multiplexed capillary electrophoresis process for substantially concurrently effecting separation in multiple fluid samples. The method comprises the steps of mounting a bundle of capillary tubes in an insulated enclosure so that inlet end portions of the tubes are spaced apart for loading of the fluid samples into the tubes and intermediate portions of the tubes are arranged in a generally planar array in which the intermediate portions extend side-by-side in closely spaced generally parallel relation. The fluid samples are loaded into the inlet end portions of the tubes, after which an electrical current is caused to flow through the contents of the capillary tubes at a level sufficient to cause separation in the fluid samples, the current generating heat in the tubes and the contents thereof. The method involves analyzing one or more properties of the fluid samples as they flow through the array of intermediate portions of the capillary tubes. The array and inlet end portions of the capillary tubes are cooled to an extent sufficient to prevent overheating of the tubes and contents thereof due to said heat. In the preferred embodiment, the closely spaced array of tubes is cooled by using a first heat transfer mechanism, and the spaced apart inlet end portions of the capillary tubes are cooled by using a second heat transfer mechanism.